title: Solid phase synthesis, radiolabeling and biological evaluation of a (99m) Tc-labeled α(V)β(3) tripeptide (RGD) conjugated to DOTA as a tumor imaging agent.
abstract: Solid phase synthesis of peptides-radiometal chelator can facilitate the creation of radioactive peptide libraries to be utilized in high throughput in in vivo screening of targeted molecular imaging agents. An α(V)β(3) tripeptide derivative DOTA-NH-Arg-Gly-Asp was synthesized by Fmoc solid phase peptide synthesis and analyzed by spectroscopic techniques. In order to radiolabel this RGD peptide with (99m)Tc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was incorporated as a chelator. The DOTA-peptide conjugate binds to (99m)Tc with high efficiency at ambient temperature. The resulting conjugate is stable under physiological conditions for at least 24 h after radiocomplexation. The receptor binding studies of (99m)Tc-DOTA- α(V)β(3)-tripeptide in established human tumor cell lines U-87MG and BMG revealed K(d) values in the nM and μM range respectively. U-87MG tumors in athymic mice were accumulated in the γ-images and major accumulation of the radiotracer was observed in kidneys followed by liver and lungs. High tumor uptake was shown in the U-87MG tumor bearing athymic mice; tumor to muscle ratios reached 8.13 ± 2.18 and 35.09 ± 4.78 at 1 and 4 h after post injection respectively.
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
authors.forename: Raunak
authors.initials: R
authors.lastname: Varshney
authors.forename: Puja Panwar
authors.initials: PP
authors.lastname: Hazari
authors.forename: Jasleen Kaur
authors.initials: JK
authors.lastname: Uppal
authors.forename: Sunil
authors.initials: S
authors.lastname: Pal
authors.forename: Roger
authors.initials: R
authors.lastname: Stromberg
authors.forename: Michele
authors.initials: M
authors.lastname: Allard
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Mishra
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004355:Drug Stability; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D011786:Quality Control; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D013667:Technetium / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D019275:Radiopharmaceuticals; D013667:Technetium; C047981:arginyl-glycyl-aspartic acid